Rubidium chloride, an alkali metal salt, has prominent effects on both brain catecholamine metabolism and behavior in animals. This drug increases the turnover of brain norepinephrine stores in rats, and facilitates expression of several types of behavior, a spectrum of activity that suggests rubidium might possess clinical antidepressant activity. The present renewal application will complete planned studies in two areas: a. rubidium's effects on catecholamine physiology and behavior, and b. rubidium's potential nephrotoxicity in rats. In the first area, we intend to complete the analysis of dosage and temporal variables on brain norepinephrine synthesis and turnover using radiolabelled tyrosyne and dopamine as norepinephrineprecursors;rubidium's effects on shuttle box avoidance behavior, and on free operant avoidance, will be compared with known antidepressant agents. With respect to the toxicological evaluation, our dog studies (in progress) have revealed no significant pathological changes; however, some suggestive evidence indicates that rubidium chloride may cause serious renal damage in rats. Therefore, we will conduct a variety of studies (clearance, transport, reabsorption) to evaluate renal function in rats, and will obtain a complete histopathological examination should renal abnormalities appear. In summary, the proposed research will approach indirectly the participation of brain norepinephrine in behavior, and will directly assess potential hazards associated with rubidium chloride administration.